The goal of the research proposed is to use a cytogenetic approach to discover new deafness genes. Many genes of the auditory system have been identified through linkage studies of families that carry deafness as a heritable trait. This process is limiting in that a large number of affected individuals need to be analyzed to gain significant data. By ascertaining deaf individuals that carry balanced translocations, it becomes possible to discover disrupted genes with the genetic material of a single person. In this proposal, I plan to study two cases where the individual is deaf and carries a balanced translocation. Using the vast number of resources available now due to the progress made by the Human Genome Project, the sequence disrupted by these translocations will be identified. This will be done by progressively narrowing the breakpoint with FISH experiments using BACs and PCR products known to hybridize in the region. Candidate genes will then be identified by comparing the disrupted sequence to those already deposited in GenBank, or by analyzing these sequences with predication programs and methods. Ultimately, a mouse mutant may be created to confirm the pathogenesis of the disrupted gene.